Genetic Variant SLC22A1:c.516-99C>T (chr6-160132133-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003057.3(SLC22A1):c.516-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,258,238 control chromosomes in the GnomAD database, including 2,424 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 635 hom., cov: 32)

Exomes 𝑓: 0.050 ( 1789 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.48

Publications

7 publications found

Variant links:

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

SLC22A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.516-99C>T	intron_variant	Intron 2 of 10	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.516-99C>T	intron_variant	Intron 2 of 9		NP_694857.1	O15245-2
SLC22A1	NM_001437335.1 link	c.516-99C>T	intron_variant	Intron 2 of 8		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.516-99C>T	intron_variant	Intron 2 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.516-99C>T		intron_variant	Intron 2 of 10	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0752

AC:

11438

AN:

152072

Hom.:

634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0719

Gnomad ASJ

AF:

0.0825

Gnomad EAS

AF:

0.0337

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0797

GnomAD4 exome

AF:

0.0504

AC:

55736

AN:

1106048

Hom.:

1789

AF XY:

0.0507

AC XY:

27873

AN XY:

549238

show subpopulations

African (AFR)

AF:

0.154

AC:

3853

AN:

24946

American (AMR)

AF:

0.0544

AC:

1527

AN:

28062

Ashkenazi Jewish (ASJ)

AF:

0.0808

AC:

1474

AN:

18240

East Asian (EAS)

AF:

0.0358

AC:

1227

AN:

34316

South Asian (SAS)

AF:

0.0685

AC:

4165

AN:

60796

European-Finnish (FIN)

AF:

0.0257

AC:

1226

AN:

47714

Middle Eastern (MID)

AF:

0.0939

AC:

444

AN:

4726

European-Non Finnish (NFE)

AF:

0.0463

AC:

38867

AN:

839878

Other (OTH)

AF:

0.0623

AC:

2953

AN:

47370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2548

5096

7645

10193

12741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1560

3120

4680

6240

7800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0753

AC:

11454

AN:

152190

Hom.:

635

Cov.:

AF XY:

0.0730

AC XY:

5435

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.148

AC:

6127

AN:

41492

American (AMR)

AF:

0.0718

AC:

1099

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

286

AN:

3466

East Asian (EAS)

AF:

0.0334

AC:

173

AN:

5178

South Asian (SAS)

AF:

0.0694

AC:

335

AN:

4824

European-Finnish (FIN)

AF:

0.0221

AC:

235

AN:

10620

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0438

AC:

2976

AN:

68002

Other (OTH)

AF:

0.0807

AC:

170

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

535

1069

1604

2138

2673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0758

Hom.:

Bravo

AF:

0.0824

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.034

(source)

DANN

Benign

0.48

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over